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Paper II — 2024 March (Supplementary) (2019 Scheme) — Q9

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Paper II
2024 March (Supplementary) (2019 Scheme) · 100 marks · 180 min

Question

Alkylating agents and their uses in cancer chemotherapy

Q94 marksShort Answers

Answer

Alkylating agents form covalent bonds with DNA (classically cross-linking guanine bases, particularly interstrand cross-links), preventing strand separation during replication and causing lethal DNA damage — cell-cycle-nonspecific, active against both dividing and resting cells.

Examples and uses:

  • Cyclophosphamide — lymphomas, leukemias, solid tumors; also used as an immunosuppressant at lower doses (severe autoimmune disease).
  • Ifosfamide — testicular cancer, sarcomas.
  • Cisplatin/Carboplatin/Oxaliplatin (platinum compounds, mechanistically alkylator-like) — testicular, ovarian, lung, and colorectal cancers.
  • Busulfan — chronic myeloid leukemia, conditioning regimens before bone marrow transplant.

Shared adverse effects: bone marrow suppression, gonadal toxicity/infertility, secondary malignancy risk with cumulative dosing; cyclophosphamide/ifosfamide specifically cause hemorrhagic cystitis (from the toxic metabolite acrolein, prevented by co-administered mesna); cisplatin specifically causes nephrotoxicity and ototoxicity.

  1. 1Cancer Chemotherapy

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